Long term exposure of saxitoxin induced cognitive deficits and YAP1 cytoplasmic retention
While most studies assessed the acute toxicity of saxitoxin (STX), fewer studies focus on the long-term degenerative effects of STX on the central nervous system. We investigated the cognitive impairment and hippocampal damages of 6 months’ exposure of low-dose STX to C57BL/6NJ mice with behavioral...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323001495 |
| _version_ | 1827989479740145664 |
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| author | Shenpan Li Xiao Chen Qian Sun Xiaohu Ren Jiacheng Zhong Li Zhou Hongyu Zhang Guowei Li Yungang Liu Jianjun Liu Haiyan Huang |
| author_facet | Shenpan Li Xiao Chen Qian Sun Xiaohu Ren Jiacheng Zhong Li Zhou Hongyu Zhang Guowei Li Yungang Liu Jianjun Liu Haiyan Huang |
| author_sort | Shenpan Li |
| collection | DOAJ |
| description | While most studies assessed the acute toxicity of saxitoxin (STX), fewer studies focus on the long-term degenerative effects of STX on the central nervous system. We investigated the cognitive impairment and hippocampal damages of 6 months’ exposure of low-dose STX to C57BL/6NJ mice with behavioral tests, H&E staining, and Western blots, and the possible mechanism (Ppp1C, YAP1, tau-phosphorylation) underlies the pathological changes. Furthermore, we discussed the specific localization of YAP1 in N2a cells induced by STX and the effect of inactivated Ppp1C on its downstream protein YAP1 in the Hippo signal pathway. We found STX intoxicated mice showed declined cognitive performance in both NOR test and MWM test, degenerations in the CA1 area of hippocampi. STX induced up-regulation expression of Ppp1C and YAP1 in hippocampus and N2a cells. Meanwhile, STX treatment induced cell apoptosis and Tau protein hyperphosphorylation. In addition, STX treatment promoted YAP1 cytoplasmic retention that indicates the activation of Hippo pathway, while depletion of Ppp1C inactivate YAP1 during the treatment of STX. Our results highlight the role of Ppp1C and YAP1 cytoplasmic retention in chronic low-dose STX intoxication. |
| first_indexed | 2024-04-10T00:20:07Z |
| format | Article |
| id | doaj.art-7c78f4ea14c34ba0968a7dae62a1d1ff |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-10T00:20:07Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-7c78f4ea14c34ba0968a7dae62a1d1ff2023-03-16T05:01:11ZengElsevierEcotoxicology and Environmental Safety0147-65132023-03-01253114645Long term exposure of saxitoxin induced cognitive deficits and YAP1 cytoplasmic retentionShenpan Li0Xiao Chen1Qian Sun2Xiaohu Ren3Jiacheng Zhong4Li Zhou5Hongyu Zhang6Guowei Li7Yungang Liu8Jianjun Liu9Haiyan Huang10Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China; Department of Toxicology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou 510515, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China; Department of Environmental and Occupational Health, Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523109, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, ChinaDepartment of Toxicology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou 510515, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China; Corresponding author.While most studies assessed the acute toxicity of saxitoxin (STX), fewer studies focus on the long-term degenerative effects of STX on the central nervous system. We investigated the cognitive impairment and hippocampal damages of 6 months’ exposure of low-dose STX to C57BL/6NJ mice with behavioral tests, H&E staining, and Western blots, and the possible mechanism (Ppp1C, YAP1, tau-phosphorylation) underlies the pathological changes. Furthermore, we discussed the specific localization of YAP1 in N2a cells induced by STX and the effect of inactivated Ppp1C on its downstream protein YAP1 in the Hippo signal pathway. We found STX intoxicated mice showed declined cognitive performance in both NOR test and MWM test, degenerations in the CA1 area of hippocampi. STX induced up-regulation expression of Ppp1C and YAP1 in hippocampus and N2a cells. Meanwhile, STX treatment induced cell apoptosis and Tau protein hyperphosphorylation. In addition, STX treatment promoted YAP1 cytoplasmic retention that indicates the activation of Hippo pathway, while depletion of Ppp1C inactivate YAP1 during the treatment of STX. Our results highlight the role of Ppp1C and YAP1 cytoplasmic retention in chronic low-dose STX intoxication.http://www.sciencedirect.com/science/article/pii/S0147651323001495SaxitoxinCognitive deficitsYAP1Hippo signaling pathway |
| spellingShingle | Shenpan Li Xiao Chen Qian Sun Xiaohu Ren Jiacheng Zhong Li Zhou Hongyu Zhang Guowei Li Yungang Liu Jianjun Liu Haiyan Huang Long term exposure of saxitoxin induced cognitive deficits and YAP1 cytoplasmic retention Ecotoxicology and Environmental Safety Saxitoxin Cognitive deficits YAP1 Hippo signaling pathway |
| title | Long term exposure of saxitoxin induced cognitive deficits and YAP1 cytoplasmic retention |
| title_full | Long term exposure of saxitoxin induced cognitive deficits and YAP1 cytoplasmic retention |
| title_fullStr | Long term exposure of saxitoxin induced cognitive deficits and YAP1 cytoplasmic retention |
| title_full_unstemmed | Long term exposure of saxitoxin induced cognitive deficits and YAP1 cytoplasmic retention |
| title_short | Long term exposure of saxitoxin induced cognitive deficits and YAP1 cytoplasmic retention |
| title_sort | long term exposure of saxitoxin induced cognitive deficits and yap1 cytoplasmic retention |
| topic | Saxitoxin Cognitive deficits YAP1 Hippo signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323001495 |
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